OP0043 IMPACT OF CARDIOVASCULAR COMORBIDITIES ON EFFICACY OF TOFACITINIB VS TNFI IN RHEUMATOID ARTHRITIS
Authors: M. H. Buch, M. Mortezavi, J. Giles, C. Charles-Schoeman, G. Karpouzas, H. Jo, K. Kwok, E. Nagy, J. L. Rivas, A. Yndestad
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patients (pts) with rheumatoid arthritis (RA) and a history of atherosclerotic cardiovascular (CV) disease (HxASCVD) have a higher risk of major adverse CV events (MACE) with tofacitinib vs tumour necrosis factor inhibitors (TNFi), whereas risk difference is not detected in pts with no HxASCVD.<sup>[1]</sup> <h3>Objectives</h3> To further explore the benefit/risk profile of tofacitinib by assessing efficacy in pts with RA with and without HxASCVD. <h3>Methods</h3> ORAL Surveillance (NCT02092467) was an open-label, post-authorisation safety study that included pts with active RA despite methotrexate treatment, aged ≥50 years and with ≥1 additional CV risk factor.<sup>[2]</sup> Pts were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or TNFi. In this post hoc analysis, pts were categorised by HxASCVD; for pts with no HxASCVD, 10-year risk of ASCVD was determined using the pooled cohort equations calculator<sup>[3]</sup> with a 1.5x multiplier applied per EULAR guidelines.<sup>[4]</sup> Odds ratios (ORs) were presented to compare tofacitinib vs TNFi in achieving remission (Clinical Disease Activity Index [CDAI] ≤2.8) or low disease activity (LDA; CDAI ≤10) at Month 6. ORs and adjusted rates of remission and LDA were obtained from a Generalised Estimating Equation repeated measures model, including baseline (BL) value, visit, treatment, treatment × visit and disease duration. <h3>Results</h3> Of 4362 pts, 640 had a HxASCVD, and 3722 had no HxASCVD, of which 3672 had BL CV scores calculated. Full pt demographics and BL disease characteristics have been published.<sup>[1,2]</sup> Mean BL CDAI scores across treatment groups ranged from 37.6–41.0 for pts with a HxASCVD or non-missing BL CV scores. ORs and the percentage of pts achieving remission and LDA with tofacitinib vs TNFi at Month 6 are shown in the Table 1 and Figure 1, respectively. ORs were greater for pts receiving tofacitinib vs TNFi in the Overall population, and in pts with no HxASCVD, and were similar in pts with a HxASCVD. Pts with high or intermediate CV risk scores tended to be more likely to reach remission or LDA with tofacitinib vs TNFi, as were pts with low–borderline risk scores who received tofacitinib 10 mg BID. <h3>Conclusion</h3> In pts with no HxASCVD, the efficacy of tofacitinib is at least as good as TNFi, and risk of MACE is comparable.<sup>[1]</sup> In pts with HxASCVD, clinicians should consider that risk of MACE with tofacitinib is higher vs TNFi,<sup>[1]</sup> while efficacy is similar. Overall, our findings further characterise the benefit/risk of tofacitinib by risk category, and provide a means to risk-stratify pts such that tofacitinib can be considered an effective treatment option where appropriate. <h3>References</h3> [1]Charles-Schoeman et al. Ann Rheum Dis 2023; 82: 119-29 [2]Ytterberg et al. N Engl J Med 2022; 386: 316-26 [3]ACC, AHA. ASCVD risk estimator https://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calulate/estimator/ [4]Agca et al. Ann Rheum Dis 2017; 76: 17-28 <h3>Acknowledgements</h3> This study was sponsored by Pfizer. Medical writing support, under the direction of the authors, was provided by Robert Morgan, PhD, CMC Connect, a division of IPG Health Medical Communications, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022; 175: 1298-1304). <h3>Disclosure of Interests</h3> Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, CESAS Medical, Eli Lilly, Galapagos, Gilead Sciences and Pfizer Inc, Grant/research support from: Gilead Sciences, Pfizer Inc and UCB, and is also supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre and is in receipt of an NIHR Senior Investigator award. All funds and honoraria paid to host institution, Mahta Mortezavi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jon Giles Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Genentech, Gilead Sciences, Novartis, Pfizer Inc and UCB, Grant/research support from: Pfizer Inc, Christina Charles-Schoeman Consultant of: AbbVie, Gilead Sciences, Pfizer Inc and Regeneron-Sanofi, Grant/research support from: AbbVie, Bristol Myers Squibb and Pfizer Inc, George Karpouzas Speakers bureau: Sanofi-Genzyme-Regeneron, Consultant of: Janssen and Sanofi-Genzyme-Regeneron, Grant/research support from: Pfizer Inc, Hyejin Jo Employee of: Syneos Health, who were paid contractors to Pfizer Inc, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Nagy Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose L. Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer SLU, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.